Circulating tumor DNA (ctDNA) monitoring in the assessment and prediction of the efficacy of PARP inhibitors (PARPi).

TPS307 Background: PARP inhibitors (PARPi) emerged as an promising treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutation. However, prediction of treatment response remains a challenge. Still, some patients with mutations other than BRCA1/2 responded to PARPi. Circulating tumor DNA (ctDNA) is a promising biomarker that can offer real-time insights into tumor dynamics, allowing for non-invasive monitoring of therapeutic efficacy. This study aims to assess ctDNA monitoring as a predictor of response and relapse for mCRPC patients receiving PARPi. Methods: This trial is an open-label, single-center, observational, prospective cohort study. This study intends to enroll 30 male mCRPC participants aged 18 to 75 years, who have progressed from second-line treatment at mCRPC stage and exhibit homologous recombination deficiency (HRD) or carrying DNA damage repair (DDR) gene mutations. The study involves whole blood and tumor tissue sampling for ctDNA detection, homologous recombination repair (HRR) gene testing, and whole exome sequencing. The primary outcomes include radiological progression-free survival (rPFS), objective response rate (ORR), and PSA response rate, with overall survival (OS) as a secondary outcome. The Institutional Review Board of Sun Yat-sen University Cancer Center approved this study. Recruitment is ongoing, with a target follow-up duration of 12 months and 26.7% (8/30) of the target sample size achieved. Data analysis is expected to commence in 2025 upon completion of recruitment. Clinical trial information: NCT05116579 .